Method and apparatus for testing blood glucose in a reversible infusion line

ABSTRACT

An apparatus for automatically and periodically measuring a patient&#39;s blood glucose level wherein the patient has a catheter in a blood vessel and is receiving infusion fluid through the catheter. A testing unit is provided which has a main infusion channel and, in a preferred embodiment, the testing unit includes a side channel. The side channel has a restrictive cross-sectional area compared with the main infusion channel. A glucose test chamber is formed in the side channel. First and second valves are placed adjacent the test chamber in the side channel to isolate a blood sample for testing. The isolation of the sample provides more accurate blood glucose measurements than those provided by systems of the prior art. A second embodiment of the invention has an isolatable test chamber placed in the main infusion line and no side channel is utilized.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of and priority from U.S.provisional applications Ser. No. 60/764,651 filed Feb. 2, 2006 and Ser.No. 60/765,851 filed Feb. 7, 2006.

BACKGROUND AND SUMMARY OF THE INVENTION

This invention relates to blood glucose testing in critically illpatients. The need for a convenient and easily applied method of glucosemonitoring in the Intensive Care Unit became evident after the landmarkstudy of Van den Berghe and colleagues published in the Nov. 8, 2001,issue of The New England Journal of Medicine.

This paper demonstrated an overall reduction in ICU patient mortality of34% when blood glucose was kept in the 80 to 110 mg per deciliter range.Samples were taken from an arterial line at 1 to 4-hour intervals andsent to the hospital lab for analysis. In the intensive therapy group,an insulin infusion was started if blood glucose exceeded 110 mg perdeciliter and was adjusted to maintain normal blood glucose levels. Avirtual flood of articles have since appeared and confirm improvedoutcomes in the treatment of various critical conditions includinginfection, stroke, in patients undergoing coronary bypass surgery, andin the treatment of myocardial infarction in both diabetic andnon-diabetic patients. One study showed greatly improved outcomes whendiabetics were monitored and treated intensively with insulin in thehospital for three days prior to undergoing coronary bypass surgery.

Intensive treatment with insulin requires knowledge of patient bloodsugar levels which presently involves obtaining either an arterial or avenous blood sample or pricking the patient's finger to obtain acapillary blood sample. Blood samples are placed on a strip and readusing a home-type glucose meter. All of these methods requireconsiderable nurse or technician time. In the U.S. at present only 20 to30% of patients in the ICU have arterial lines. Many patients,especially non-diabetics, find repeated finger sticks objectionable.Furthermore, intermittent blood samples may not be done often enough togive an accurate picture of blood sugar levels.

Optimally, patients in critical care situations should have bloodglucose levels monitored several times each hour so that insulin can begiven appropriately to keep blood sugar readings in the narrow range of80-110 mg/deciliter. Presently there is no system available thataccurately and conveniently measures blood sugar without taking frequentblood samples from a patient. The present invention is able to do so bywithdrawing blood from a central venous line, an arterial line or acatheter in a peripheral vein. The catheterized blood vessel in any ofthese locations is normally used for infusion of fluids withelectrolytes or various medications. The present invention also allowsthese lines to monitor a patient's blood sugar as often as every threeminutes so that a care giver can adjust insulin dosage as required.

Attempts have been made in the past to automatically monitor bloodanalytes from a patient's IV line. Generally these systems have usedreversal of the direction of flow in an infusion line so that bloodcould be pulled out of the patient's circulation at intervals, analyzed,and then re-infused back into the patient. Examples of such device aredescribed in U.S. Pat. No. 3,910,256 to Clark, U.S. Pat. No. 4,573,968to Parker and U.S. Pat. Nos. 5,165,406, 5,758,643 and 5,947,911 to Wongand associates.

The devices described in the above patents measure blood analytes withsensors inside the main infusion line and no attempt has been made toisolate or compartmentalize blood samples during testing. Thistechnique, while successful for monitoring blood gases, has not yet metwith success in testing for blood glucose. The present invention, bynovel means, allows practical and accurate monitoring of blood sugarfrom a reversible infusion line.

State of the art blood glucose measuring systems generally employ theenzymes glucose oxidase or glucose dehydrogenase. In the chemicalreaction which occurs using either of these two enzymes, glucose isconsumed and the electrons generated are drawn off and measured.Plotting current flow against time produces a curve which is distinctivefor each glucose value, i.e., any given concentration level of bloodglucose.

Accuracy depends crucially on maintaining a constant diffusion gradientover the glucose sensor. In the ideal case the concentration of glucosevaries in a regular and linear way from the body's reservoir of bloodglucose to the area just over the sensor where concentration drops to aminimum (close to zero) because it is being consumed in the chemicalreaction. The major cause of inaccuracy in electrochemical glucosemeasurement is disturbance of the diffusion gradient. The problem isrelatively small in single use disposable strips because a portion of ablood drop is allowed to rest undisturbed in a small channel during thetest, having been drawn up into the channel by capillary attraction. Ina flow-through system the problem of leaving the diffusion gradientundisturbed is a major one because of the much larger volume of fluidinvolved, which is essentially all the fluid in the infusion line fromthe patient to the bedside monitor.

A disturbance anywhere in this large reservoir of fluid is immediatelytransmitted to the test area and causes disturbance of the diffusiongradient over the sensing electrode. Invariably, the effect is to bringmore glucose to the region of the electrode, causing an increase in theglucose signal and an overestimation of blood glucose.

A number of causes can contribute to disruption of the diffusiongradient in a flow through system. Any fluid movement, even a flow rateas low as 150 micro liters/minute, can cause a mixing effect whichdisturbs the diffusion gradient and gives an overestimation of bloodglucose. Eddies in the fluid line can occur because of the intermittent“push” of a peristaltic pump. Such eddies can last several seconds afterpumping has stopped.

Adjustment of blood temperature to ambient temperature can cause microfluidic deviations which will disturb the diffusion gradient. Heattransfer issues are minimized by keeping the amount of fluid small incomparison to the total mass of the device. The device can be subjectedto temperature controls but under practical conditions small volumes arerequired to prevent temperature differences from causing significantmeasurement errors. The diffusion gradient over the sensor can also bedisturbed in an open-flow system by movement of the arm or chest, orchanges in the relative position of the test chamber and the heart.Additionally, impacts to the tubing or glucose test area can causemeasurement inaccuracies if the fluid in the test area is not protectedin a small, well defined space.

For complete isolation, small valves, which may be inflatable balloons,can be located adjacent the test chamber. Besides protecting thediffusion gradient, isolation of the test sample prevents movement ofglucose molecules into or out of the test area and allows consistentmeasurement of the current produced during the reaction at any givenglucose level.

In the present invention, the test chamber for testing blood glucose caneither be part of the main infusion line inside the testing unit, or itcan be located in a side channel in the testing unit in continuity withthe main channel. In the latter version, a valve, which may be aninflatable balloon, directs blood or fluid into the side channel at thetime of testing. For reasons to be enumerated, the side channel versionis considered the preferred embodiment of the invention.

The system to be described uses a bedside monitor with a digital readoutand alarms and contains two peristaltic pumps, one of which normallyinfuses fluid through the blood vessel catheter. During glucose testingthe pump assists in moving blood samples into and out of the testchamber. The second peristaltic pump automatically calibrates the sensorat intervals with a premixed calibration fluid.

The disposable, single patient use testing unit is approximately2¼″×1½″×¾″ and is attached to the patient's chest for use with a centralline or to an extremity for use with a catheter in a peripheral vessel.The distal end of the testing unit has an integral Luer fitting whichconnects to the patient's blood vessel catheter. The proximal end of thetesting unit has the exit sites for the fluid, air, and electric linesthat connect to a bedside monitor located a few meters from the patient.

The disposable testing unit portion of the invention is made of asemi-transparent plastic. It contains a channel for infusion fluid incontinuity with (i.e. in fluid communication with) the infusion line andwith the blood vessel catheter. A glucose sensing electrode is locatedin the test chamber area of the testing unit. Chambers for inflatableballoons, which serve as valves, are molded into the plastic parts alongwith grooves for the air lines and the electric cable. After insertionof the various components during manufacturing, the top and bottomhalves are welded together to form a leak proof disposable testing unit.While inflatable balloons are considered the preferred embodiment forreasons of economy and ease of insertion, mechanical valves can also beused for this application.

The sensor of the present invention can be automatically calibrated atselected intervals using a small bag of premixed calibration fluid whichis supplied with each disposable testing unit. The calibration fluid iscarried inside the monitor and made to flow through the test chamber atintervals by a second peristaltic pump. After calibration is completethe test chamber is cleared by a brief flow of infusion fluid throughthe sampling area.

The area of the glucose sensor in the present invention is approximately25 square millimeters, considerably larger than that of a typicaldisposable strip. The height of the test chamber's is from 0.3 to 0.5mm, giving a fluid volume in the chamber of 8 to 12 micro liters. Thelarge electrode described herein is thought advantageous in thisspecific application because of the large amount of current producedduring a test. Current from a 25 sq. millimeter sensor will be measuredin micro amps rather than the nano amps of some single use strips. Alarge current flow is advantageous for optimum resolution of the signal.

In the present invention, the openings into the test chamber are atleast 300 microns in height, which duplicate the height of the testchamber. Blood is quite viscous and this minimum height is necessary toallow adequate blood flow in and out of the test chamber. Positivepressure is still required to bring blood or fluid into the test chamberand for the same reason pressure is needed to clear the site once thetest has been performed. The present invention is capable of exertingadequate pressure to draw in the sample or flush it from the testchamber.

In the descriptions and drawings to follow, two embodiments of theinvention are shown. The first embodiment has its test chamber locateddirectly in the main infusion line. The second embodiment has the testchamber located in a side channel, in continuity with the main channel.Several advantages accrue to the side channel version. Firstly, anunrestricted main channel (used together with a restricted side channel)allows for the rapid flow of fluid through the device most of the time.Secondly, a constant flow of fluid through the test chamber (if no sidechannel is used) could disperse the reagents necessary for repeatedtesting of blood glucose. This problem is avoided, in the preferredembodiment, since infusion fluid usually flows through the main channel.Thirdly, in the non-side channel version, a large volume of blood mustbe forced through the test chamber so that an undiluted sample isadjacent the sensor. Damage to red cells can occur when forcing a largequantity of blood through a very small opening. By contrast, in the sidechannel version blood can be easily withdrawn from the patient throughthe unobstructed main channel until a pure sample is opposite the testsite. At that time only a very small quantity of blood need be directedinto the side channel for testing.

It should be emphasized that a controllable valve in the main channel isan essential aspect of the side channel version of the invention.Without controlled blockage of the main channel, blood and fluids wouldalways take the path of least resistance through the main channel andnever enter the side channel.

In the following description of the present invention, the one or morevalves inside the device are comprised of inflatable balloons. It is tobe understood that mechanical valves of various types could also be usedin this application. Inflatable balloons are considered the preferredembodiment for reasons of economy and for ease of insertion duringassembly.

In the examples to follow, traditional monitoring in an open-flow systemis compared to testing with the preferred embodiment of the presentinvention. Monitoring blood sugar in a conventional flow-through systemis possible if there is no disturbance of the diffusion gradient overthe sensing electrode. In reality, such disturbances occur constantlyfor the several reasons mentioned. In a flow-through system in whichblood or fluid is propelled by a peristaltic pump, the cog-wheel effectis very evident and causes confusing variations to the glucose diffusiongradient. Additionally, a peristaltic flow-through system is subject toall the additional artifacts contributed by impacts to the infusion bag,the tubing and the sensor itself. Clearly a sensor which isolates thetest fluid and keeps it completely at rest is best able to maintain astable diffusion gradient and give the most accurate estimation of bloodglucose.

No references in the prior art have been found to methods of isolatingsmall extra corporal samples for testing. Therasense U.S. Pat. No.6,120,676 states that a sensor for blood glucose can be used in aflowing sample stream which is made to flow through a sampling chamber.No method is described of sample isolation although the authors statethat the sample can be made to flow at a slow rate. In claim 32 of thesame patent the authors mention holding the sample stationary in asampling chamber but the latter is on a disposable strip and not in areversible infusion line where the sensor must test repeatedly over aperiod of days.

An advantage of the present invention is to put blood in contact withthe sensor only briefly during each test. Following the test, the testchamber in the testing unit is flushed with clear fluid which reducesprotein and fibrin deposition on the sensing membrane. For example, if aglucose test takes 20 seconds and readings are done every five minutes,then blood will be in contact with the sensor only about 3% of the totalelapsed time.

A primary object of the invention is to provide a system for repeatedmonitoring of blood glucose from an ordinary infusion line with anaccuracy approaching that of a clinical lab.

A further object of the invention is to attain such accuracy byisolation of the test sample during a test.

A further object of the invention is a system usable with equal ease ineither a peripheral vein or a central venous line.

A further object of the invention is to provide a small disposabletesting unit which is attachable to either the chest for proximity to acentral line or to an extremity for use with a peripheral vein.

A further object of the invention is to provide a system which isautomatically and periodically self-calibrating.

Other objects and advantages of the invention will become apparent fromthe following description and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overall view of the present invention used in conjunctionwith a patient;

FIG. 2 is a perspective view of the disposable testing unit of thepresent invention attached to a patient's forearm;

FIG. 3 is a close-up view of the bedside monitor showing the variousleads and attachments;

FIG. 4 is a cross-sectional plan view of a first embodiment of thedisposable testing unit shown actual size;

FIG. 5 is the same view as shown in FIG. 4 but expanded to twice actualsize for clarity;

FIG. 6 is a cross-sectional view on the line 6-6 of FIG. 5; balloonvalves adjacent to the reaction chamber are partially inflated;

FIG. 7 is the same view as FIG. 6 with balloon valves fully inflated;

FIG. 8 is a schematic illustration of the first step of obtaining ablood sample using the device shown in FIGS. 5-7; in FIG. 8 the balloonvalves are closed and the infusion pump is reversed drawing bloodbackwardly through the testing unit;

FIG. 9 is a schematic showing the second step of the process wherein theballoon valves are closed and the blood sample in the test chamber isbeing tested for glucose levels;

FIG. 10 shows the next step in the process wherein the balloon valvesare opened and the peristaltic pump is pumping infusion fluid throughthe test chamber;

FIGS. 11-20 are schematic illustrations of the second, preferredembodiment of the invention, illustrating the steps of performing theglucose testing according to the invention;

FIG. 11 is a cross-sectional plan view of the second embodimentincorporating a side channel in the testing unit, shown approximatelyactual size;

FIG. 12 is the same schematic and plan view of FIG. 11 shownapproximately twice actual size for clarity; as shown in FIG. 12,infusion fluid is flowing through the main infusion line towards thecatheter in the patient's blood vessel;

FIG. 13 illustrates the infusion pump operating in the reverse orbackward direction and causing blood to flow backwardly through thetesting unit through the main infusion channel, with the balloon valvein the main infusion channel in its open position;

FIG. 14 shows the balloon valve in the main channel closed, therebycausing blood to be pumped by the infusion pump through the side channeland wherein the balloon valves adjacent the test chamber are opened toallow blood to fill the test chamber;

FIG. 15 shows the testing unit when the glucose level is actually beingtested, wherein the balloons adjacent the test chamber are closed andisolate the blood sample;

FIG. 16 shows the flushing of the main channel shortly after the testhas been performed in the test chamber wherein the balloon valve in themain channel is opened and infusion fluid is being pumped through themain channel toward the patient;

FIG. 17 illustrates the flushing or cleansing of the test chamber withcalibration fluid, showing the valves adjacent the test chamber openedand the valve controlling calibration fluid opened and the valve in themain infusion channel is closed to force the calibration fluid to flowthrough and flush the test chamber;

FIG. 18 illustrates all four balloon valves closed after the testchamber has been flushed with calibration fluid, allowing the testchamber to be recalibrated;

FIG. 19 illustrates the reintroduction of infusion fluid through theside channel after the calibration fluid has been pumped through theside channel for calibration purposes;

FIG. 20 illustrates reintroduction of infusion fluid through the mainchannel;

FIGS. 21-25 illustrate a series of glucose consumption curves andillustrate the significance of utilizing the “stable diffusion gradient”of the present invention compared with prior art glucose consumptioncurves;

FIG. 21 illustrates glucose consumption curves under ideal conditionsutilizing a stabilized diffusion gradient according to the invention forfive different blood glucose concentration levels;

FIG. 22 is a glucose consumption curve (or current flow curve) utilizingthe stable diffusion gradient technique of the present invention for onegiven blood glucose level;

FIG. 23 illustrates a prior art glucose consumption curve whereinperturbations or disturbances caused by coughing or other chest motionof the patient will produce an erroneously high blood glucose reading;

FIG. 24 illustrates a glucose consumption curve or current flow curvewhere the isolation techniques of the present invention are utilized andwherein coughing or chest motion of the patient has very little, if any,effect on the blood glucose measurement;

FIG. 25 is a pair of glucose consumption curves illustrating how a slowflow rate of blood through a non-isolated prior art test chamber stillproduces an erroneously high blood glucose measurement; and

FIG. 26 is a pair of glucose consumption curves illustrating how a slowflow rate of blood pumped through a non-isolated prior art test chamberby a peristaltic pump will produce a varying and erroneously high bloodglucose measurement.

DETAILED DESCRIPTION OF THE DRAWINGS

FIGS. 1, 2 and 3 illustrate the overall environment of the invention. Ahospitalized patient 9 typically in an ICU unit is shown with adisposable testing unit 50 of the present invention attached to forearm8 by a Coban elastic band 7. A catheter 45 is shown inserted into apatient blood vessel on the back of the patient's hand. A first infusionline 21 connects catheter 45 to testing unit 50. A source of infusionfluid is shown as IV bag 20 suspended from a support 19 as is known inthe art. Infusion fluid 25 stored in infusion bag 20 passes downwardlythrough a second infusion line 22 and through a reversible peristalticpump 40 carried in monitor housing 30. The second infusion line 22continues downwardly from peristaltic pump 41 and enters the test unit50. The infusion fluid passes through testing unit 50 as described indetail below and through first infusion line 21 that extends fromtesting unit 50 to catheter 45 and provides infusion fluid into thepatient's blood vessel. When the reversible peristaltic pump 40 isoperating in its ordinary forward mode infusion fluid 21 from source 20is pumped through infusion line 22 and through testing unit 50 and thenthrough the lower connector 52 which attaches to IV catheter 45. Whenthe peristaltic pump is reversed and pumps infusion fluid and bloodbackwardly through attached unit 50 an undiluted blood sample becomesavailable for testing. The presence of an undiluted blood sample ispreferably determined by the optical method described in U.S. patentapplication Ser. No. 11/228,827 filed on Sep. 16, 2005, incorporatedherein by reference. Electrical power is fed to testing unit 50 by line100 extending from monitor 30.

Air lines 201, 202 and 203 are shown here as separate lines but inactuality are part of a triple-lumen tube which is permanently embeddedin the proximal end of the testing unit 50 but attachable to the monitor30 at the time of set-up. These lines carry air from motor-drivenprecision syringes to inflate or deflate small balloon valves inside thetesting unit 50. Three air lines suffice when four balloons are used inthe disposable testing unit 50 because two balloons adjacent the sensingchamber are always inflated or deflated at the same time.

A bag of pre-mixed calibration fluid (not shown) is situated inside themonitor and a second fluid line 205 runs from the calibration fluid bagover a second peristaltic pump 41 to reach the testing unit 50 near theentrance of main infusion line 22. Monitor 30 has a screen 31 thatdisplays the blood glucose level from the most recent test. An accessdoor 35 located adjacent to screen 31 opens to allow access to bothperistaltic pumps (shown in phantom), replacement or removal of theinfusion and calibration lines along with the bag of pre-mixedcalibration fluid.

FIGS. 4-10 illustrate a first embodiment of the invention, wherein thetesting unit 50 has a single main infusion passageway and no sidechannel.

FIG. 4 is a schematic sectional view along the line 4-4 of FIG. 2. TheLuer connector 52 is permanently attached to the distal end 50 a of thetesting unit 50 and is in continuity with infusion channel 120. Narrowslits 58 and 59 are approximately 300 microns high and 5 millimeterswide open to the proximal and distal portions of the main channel 120.Glucose sensor 12 rests on the bottom of test chamber 15 which holdsfluid for testing. Dimensions of the test chamber 15 are 5 mm×5 mm×300microns. Sensor 12 is connected by cable 100 to the electronics of thebed side monitor 30. First and second valves 81 and 82 are situated inthe main infusion line 120 and rest in balloon chambers 91 and 92.

FIG. 5 is simply an enlargement of FIG. 4 to twice actual size forclarity.

FIG. 6 is a sectional view on the line 6-6 of FIG. 5. The inflatableballoon valves 81 and 82 are shown partially inflated. Small diametercatheters 101 and 102 enter balloon chambers 91 and 92 transversely tomain infusion line 120 and then make a right angle turn to exit at theproximal end 50 b of the testing unit 50.

FIG. 7 is the same view as FIG. 6 but now shows the balloon valves 81and 82 fully inflated to block the entrances to the test chamber 15.While for clarity a small space is drawn between the balloon and theballoon chamber's inner wall, in reality the balloon is under sufficientpressure to be tightly applied to the chamber wall in order to block allfluid movement.

FIGS. 8, 9 and 10 are schematic views similar to FIGS. 4 and 5 showingoperation of the first embodiment of the invention when testing forglucose. In FIG. 8, peristaltic flow has been reversed to withdraw bloodfrom a patient. When it has been determined that a pure sample of bloodis in contact with the glucose electrode 12, the peristaltic pump isstopped and balloons 81 and 82 are inflated, as shown in FIG. 9, and ameasurement is taken. It is significant to note that, as shown in FIG.9, first and second balloon valve 81,82 are adjacent test chamber 15 andon opposite sides of test chamber 15. The blood sample in test chamber15 (and test chamber 15 itself), as shown in FIG. 9, are isolated fromall other fluid channels in testing unit 50, i.e., main infusion channel120. Fluid communication between test chamber 15 and other fluidchannels (i.e., main channel 120) is temporarily blocked. Forwardpumping of the infusion fluid, with the balloons 81,82 deflated, asshown in FIG. 10, clears the test chamber 15 of blood.

As shown in FIG. 10, after the testing of the sample, first and secondballoon valves are opened.

FIGS. 11-20 illustrate a second, preferred embodiment of the inventionwherein the testing unit 250 includes a main infusion channel orpassageway 320 and a novel side channel 420. The side channel 420includes test chamber 215 having electrode 212. First and second balloonvalves 281 and 282 are located in side channel 420 and are adjacent testchamber 215 and on opposite sides of test chamber 215. A third balloonvalve 283 is located in main channel 320. Closing of third valve 283causes infusion fluid and/or blood to flow through side channel 420.Side channel 420 is more restrictive in cross-sectional area than mainchannel 320 as described above. A fourth balloon valve 284 is located incalibration fluid channel 460; calibration fluid channel 460 is in fluidcommunication with side channel 420. Opening fourth valve 284 allowscalibration fluid to enter side channel 420 and to flush test chamber215 (with valves 281,282 open and valve 283 closed). Test chamber 215has a volume between 8 μL and 12 μL and a cross-sectional height greaterthan 300 microns, as noted above.

FIG. 11 is a sagittal view along the central plane of a second versionof the testing unit 250, drawn to its actual size, which is 2¼″×1½″ by¾″. The connector 252 is permanently attached to the distal end 205 a ofthe testing unit 250 and is in continuity with main infusion channel 320and side channel 420. Inflatable balloon valves 281, 282, 283 and 284rest in balloon chambers 291, 292, 293 and 294. Two narrow slits 420 aand 420 b, approximately 300 microns high, connect the proximal anddistal ends of the side channel through the two balloon chambers 291 and292. Glucose sensor 212 rests at the bottom of the test chamber 215wherein the top of the sensor makes contact with fluid to be tested.Sensor 212 is connected by cable 300 to the electronics of the bedsidemonitor.

FIG. 12 is the same view as shown in FIG. 11, enlarged approximately 2×.All balloon valves (281, 282 and 284) except the main channel balloon283 in the balloon chamber 293 are inflated, closing the valves. Normalflow of infusion fluid through the main channel 320 is shown in thisdrawing. Patient blood vessel catheter (not shown) is attached to luerconnector 252.

FIG. 13 shows blood being drawn from the patient by reversing theperistaltic pump. Reverse pumping is stopped when the optics (not shown)of the testing unit 250 indicate that undiluted blood is now in the testchamber 215.

FIG. 14 shows the balloon 281 of the main channel 320 now completelyinflated and closed. Reverse peristaltic pumping now draws blood intothe side channel 420 and into the test chamber 215. It should beappreciated that a controllable valve 283 in the main channel 320 is anessential aspect of the invention. Without controlled blockage of themain channel, fluid could not be forced through the restricted sidechannel 420 and fluids would always take the path of least resistancethrough the main channel 320.

FIG. 15 shows all, four balloons inflated and peristaltic pumpingstopped for approximately 20 seconds while the blood in test chamber 215over the sensor 212 is tested. Both entrances to the test chamber 215are temporarily completely blocked by the inflated first and secondballoons 281,282 so that the glucose diffusion gradient over the sensor212 is not perturbed during the test. The test chamber 215 and the bloodsample therein are isolated from other fluid channels in testing unit250.

FIG. 16 shows the flushing of the main channel 320 shortly after thetest has been performed in the test chamber 215 wherein the balloonvalve 283 in the main channel is opened and infusion fluid is beingpumped through the main channel toward the patient.

FIG. 17 illustrates the flushing or cleansing of the test chamber 215with calibration fluid showing the valves 281,282 adjacent the testchamber 215 opened and the valve controlling calibration fluid openedand the valve 283 in the main infusion channel 320 is closed to forcethe calibration fluid to flow through and flush the test chamber.

FIG. 18 illustrates all four balloon valves closed after the testchamber 215 has been flushed with calibration fluid, allowing the testchamber to be recalibrated.

FIG. 19 illustrates the reintroduction of infusion fluid through theside channel 420 (with valves 281,282 open and valves 283,284 closed)after the calibration fluid has been pumped through the side channel forcalibration purposes.

FIG. 20 illustrates reintroduction of infusion fluid through the mainchannel 320 (with valve 283 open, valves 281,282 and 284 closed).

FIGS. 21-25 illustrate a series of glucose consumption curves andillustrate the significance of utilizing the “stable diffusion gradient”of the present invention compared with prior art glucose consumptioncurves.

FIG. 21 illustrates glucose consumption curves under ideal conditionsutilizing a stabilized diffusion gradient according to the invention forfive different blood glucose concentration levels.

FIG. 22 is a glucose consumption curve (or current flow curve) utilizingthe stable diffusion gradient technique of the present invention for onegiven blood glucose level.

FIG. 23 illustrates a prior art glucose consumption curve whereinperturbations or disturbances caused by coughing or other chest motionof the patient will produce an erroneous blood glucose reading.

FIG. 24 illustrates a glucose consumption curve or current flow curvewhere the isolation techniques of the present invention are utilized andwherein coughing or chest motion of the patient has very little, if any,effect on the blood glucose measurement. Small and insignificantartifacts are sometimes seen, marking the points where much largerchanges in the curve would occur without test chamber isolation.

FIG. 25 illustrates a first glucose consumption curve 310 obtained byutilizing the isolated test chamber of the present invention. FIG. 25also includes a second glucose consumption curve 320 that is obtained ifthe test chamber is not isolated according to the present invention, butwhere a very slow flow rate of 150 μL/minute of fluid is allowed to passinto or through the test chamber during a test. The second curve 320results in a 20% overestimation of glucose concentration.

FIG. 26 illustrates a first glucose consumption curve 410 obtained byutilizing the isolated test chamber of the present invention. FIG. 26also includes a second glucose consumption curve 420 obtained if thetest chamber is not isolated according to the present invention, butwhere a peristaltic pump is slowly pumping fluid at 150 μL/minute intoor through the test chamber. Curve 420 illustrates the “cog wheel” orpulsating effect of such a pump. Curve 420 also illustrates howerroneously high blood glucose measurements are obtained if the testsample is not isolated and small amounts of fluid are allowed to beslowly pumped into or through the test chamber during a test. Theglucose measurement induced by 150 μL/minute flow is approximately 20%higher than the correct value due to disruption of the diffusiongradient.

The foregoing description of the invention has been presented forpurposes of illustration and description and is not intended to beexhaustive or to limit the invention to the precise form disclosed.Modifications and variations are possible in light of the aboveteaching. The embodiments were chosen and described to best explain theprinciples of the invention and its practical application to therebyenable others skilled in the art to best use the invention in variousembodiments and with various modifications suited to the particular usecontemplated. The scope of the invention is to be defined by thefollowing claims.

1. An apparatus for automatically and periodically measuring a patient'sblood glucose level comprising: a testing unit, infusion lines toconnect said testing unit to a source of infusion fluid and to acatheter placed in a patient's blood vessel, reversible peristaltic pumpmeans to move infusion fluid or blood either forwardly through saidtesting unit into said blood vessel catheter or backwardly into saidtesting unit and said infusion line, a main channel for blood orinfusion fluid within said testing unit, a side channel in the testingunit connected to said main channel, a test chamber within said sidechannel for glucose testing, and valve means for controlling fluid flowthrough said main channel and isolating said test chamber in said sidechannel, wherein said valve means includes first and second valves insaid side channel for isolating a blood sample in said test chamber,said first and second valves being adjacent to and on opposite sides ofsaid test chamber, further comprising third valve means in said mainchannel for diverting fluid flow into said side channel, furthercomprising a calibration fluid channel in fluid communication with saidside channel and fourth valve means in said calibration fluid channel toallow calibration fluid to flow through said side channel and said testchamber, wherein each of said valve means is a balloon valve.